UHMK1 Is a Novel Marker for Personalized Prediction of Pancreatic Cancer Prognosis

Luo, Yiqiao; Han, Shanshan; Yan, Bin; Ji, Huihui; Zhao, Lei; Gladkich, Jury; Herr, Ingrid

doi:10.3389/fonc.2022.834647

Cited by 7 publications

(9 citation statements)

References 46 publications

(63 reference statements)

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“…Furthermore, UHMK1 knockdown reduced migration, while UHMK1 overexpression increased migration. These results are in line with previous reports, showing that modulation of UHMK1 affects cell migration, colony formation, and proliferation ( 13 , 16 , 25 ) and further support the data that UHMK1 regulates the phosphorylation of protein networks governing these cellular processes.…”

Section: Discussionsupporting

confidence: 93%

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UHMK1 is a novel splicing regulatory kinase

Arfelli¹,

Chang²,

Bagnoli³

et al. 2023

Journal of Biological Chemistry

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Section: Discussionsupporting

confidence: 93%

“…By reprogramming the nucleotide metabolism through the UHMK1–NCOA3–ATF4 axis, UHMK1 contributes to gastric cancer ( 24 ). Also, the involvement of UHMK1 in pancreatic and colon cancers was recently reported ( 25 , 26 ).…”

mentioning

confidence: 89%

UHMK1 is a novel splicing regulatory kinase

Arfelli¹,

Chang²,

Bagnoli³

et al. 2023

Journal of Biological Chemistry

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“…Furthermore, UHMK1 knockdown reduced migration, while UHMK1 overexpression increased migration. These results are in line with previous reports, showing that modulation of UHMK1 affects cell migration, colony formation, and proliferation [12,15,24], and further support the data that UHMK1 regulates the phosphorylation of protein networks governing these cellular processes.…”

Section: Discussionsupporting

confidence: 93%

“…By reprogramming the nucleotide metabolism through the UHMK1-NCOA3-ATF4 axis, UHMK1 contributes to gastric cancer [23]. Also, the involvement of UHMK1 in pancreatic cancer was reported [24].…”

Section: Introductionmentioning

confidence: 99%

UHMK1 is a novel splicing regulatory kinase

Arfelli

Chang

Bagnoli

et al. 2022

Preprint

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The U2AF Homology Motif Kinase 1 (UHMK1) is the only kinase that contains the U2AF homology motif (UHM), a common protein interaction domain among splicing factors. Through this motif, UHMK1 interacts with the splicing factors SF1 and SF3B1, known to participate in the 3’ splice site recognition during the early steps of spliceosome assembly. Although UHMK1 phosphorylates these splicing factors in vitro, the involvement of UHMK1 in RNA processing has not previously been demonstrated. Here, we identify novel putative substrates of this kinase and evaluate UHMK1 contribution to overall gene expression and splicing, by integrating global phosphoproteomics, RNA-seq, and bioinformatics approaches. Upon UHMK1 modulation, 163 unique phosphosites were differentially phosphorylated in 117 proteins, of which 106 are novel potential substrates of this kinase. Gene Ontology (GO) analysis showed enrichment of terms previously associated with UHMK1 function, such as mRNA splicing, cell cycle, cell division and microtubule organization. The majority of the annotated RNA-related proteins are components of the spliceosome, but are also involved in several steps of gene expression. Comprehensive analysis of splicing showed that UHMK1 affected over 200 alternative splicing events. Moreover, splicing reporter assay further supported UHMK1 function on splicing. Overall, RNA-seq data demonstrated that UHMK1 knockdown had a minor impact on gene expression and pointed to UHMK1 function in epithelial-mesenchymal transition. Finally, the functional assays demonstrated that UHMK1 modulation affects proliferation, colony formation, and migration of the cells. Taken together, our data implicate UHMK1 as a splicing regulatory kinase, connecting protein regulation through phosphorylation and gene expression in key cellular processes.

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“…Research on UHMK1 was initially focused on neurological diseases such as schizophrenia 17 , 18 because of its abundant expression in the nervous system. 19 In the last few years, many researches have revealed the function of UHMK1 in promoting the initiation and progression of different types of cancer, including ovarian cancer, 20 , 21 melanoma, 22 , 23 cervical cancer, 24 liver cancer, 25 , 26 colorectal carcinoma, 27 , 28 pancreatic cancer, 29 , 30 , 31 and gastric cancer. 32 However, no studies have investigated the function and regulatory mechanism of UHMK1 in LUAD.…”

Section: Introductionmentioning

confidence: 99%

UHMK1 promotes lung adenocarcinoma oncogenesis by regulating the PI3K/AKT/mTOR signaling pathway

Wang

Jin

et al. 2023

Thoracic Cancer

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Background Effective targeted therapy for lung adenocarcinoma (LUAD), the number one cancer killer worldwide, continues to be a difficult problem because of the limitation of number of applicable patients and acquired resistance. Identifying more promising drug targets for LUAD treatment holds immense clinical significance. Recent studies have revealed that the U2 auxiliary factor (U2AF) homology motif kinase 1 (UHMK1) is a robust pro‐oncogenic factor in many cancers. However, its biological functions and the underlying molecular mechanisms in LUAD have not been investigated. Methods The UHMK1 expression in LUAD cells and tissues was evaluated by bioinformatics analysis, immunohistochemistry (IHC), western blotting (WB), and real time quantitative polymerase chain reaction (RT‐qPCR) assays. A series of gain‐ and loss‐of‐function experiments for UHMK1 were carried out to investigate its biological functions in LUAD in vitro and in vivo. The mechanisms underlying UHMK1's effects in LUAD were analyzed by transcriptome sequencing and WB assays. Results UHMK1 expression was aberrantly elevated in LUAD tumors and cell lines and positively correlated with tumor size and unfavorable patient prognosis. Functionally, UHMK1 displayed robust pro‐oncogenic capacity in LUAD and mechanistically exerted its biological effects via the phosphoinositide 3‐kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) signaling pathway. Conclusion UHMK1 is a potent oncogene in LUAD. Targeting UHMK1 may significantly improve the effect of LUAD treatment via inhibiting multiple biological ways of LUAD progression.

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UHMK1 Is a Novel Marker for Personalized Prediction of Pancreatic Cancer Prognosis

Cited by 7 publications

References 46 publications

UHMK1 is a novel splicing regulatory kinase

UHMK1 is a novel splicing regulatory kinase

UHMK1 is a novel splicing regulatory kinase

UHMK1 promotes lung adenocarcinoma oncogenesis by regulating the PI3K/AKT/mTOR signaling pathway

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